complete hiv 1/2

Read this Product Insert completely before using the product. Follow the instructions carefully when performing the test as not doing so may result in inaccurate Test Results. Users of this test should follow the CDC Universal Precautions for prevention of transmission of Human Immunodeficiency Virus, Hepatitis B Virus, and other blood borne pathogens.1

CLIA Complexity: WAIVED FOR FINGERSTICK WHOLE BLOOD AND VENIPUNCTURE WHOLE BLOOD. ANY MODIFICATION BY THE LABORATORY TO THE TEST SYSTEM OR FDA APPROVED TEST SYSTEM INSTRUCTIONS WILL RESULT IN THE TEST NO LONGER MEETING THE REQUIREMENTS FOR WAIVED CATEGORY.

CLIA Complexity: MODERATE FOR SERUM AND PLASMA SAMPLES.

Storage: Store at 8° to 30°C (46° to 86°F)

NAME AND INTENDED USEThe Clearview® COMPLETE HIV 1/2 assay is a single-use immunochromatographic test for the detection of antibodies to Human Immunodeficiency Virus Types 1 (HIV-1) and Type 2 (HIV-2) in fingerstick whole blood, venous whole blood, and serum or plasma specimens. The Clearview® COMPLETE HIV 1/2 assay is intended for use as a point-of-care test to aid in the diagnosis of infection with HIV-1 and HIV-2. This test is suitable for use in multi-test algorithms designed for the statistical validation of rapid HIV test results. When multiple rapid HIV tests are available, this test should be used in appropriate multi-test algorithms.

RESTRICTIONS• SaleoftheClearview®COMPLETEHIV1/2assayisrestrictedtoclinicallaboratoriesthathave an adequate quality assurance program, including planned systematic activitiesthatprovideadequateconfidencethatrequirementsforqualitywillbemetandwherethereisassurancethatoperatorswillreceiveandusetheinstructionalmaterials.

• TheClearview®COMPLETEHIV1/2assayisapprovedforuseonlybyanagentofaclinicallaboratory.

• Non-clinical testingsites thatofferwaived rapidHIV testsmusteitherhave theirownCLIACertificateofWaiverorhaveanagreementtoworkundertheCLIACertificateofanexistinglaboratory.

• Testsubjectsmustreceivethe“SubjectInformationNotice”priortospecimencollectionandappropriateinformationwhentestresultsareprovided.

• TheClearview®COMPLETEHIV1/2assayisnotapprovedforusetoscreenblood,plasma,cellortissuedonors.

SUMMARY AND EXPLANATION OF THE TESTDiscovered in 1983, the Human Immunodeficiency Virus is a retrovirus and identified as the etiologic agent for the Acquired Immunodeficiency Syndrome (AIDS), and AIDS related complex2. AIDS is characterized by changes in the population of T-cell lymphocytes that play a key role in the immune defense system. In the infected individual the virus causes a depletion of a subpopula-tion of T-cells, called T-helper cells, which leaves these patients susceptible to opportunistic infec-tions and certain malignancies. The major routes of transmission are sexual contact, exposure to contaminated blood or blood products (including sharing of contaminated syringes and needles) and mother-to-newborn transmission.3-5

Although there has been a decrease in the rate of infection in certain countries, the number of persons infected with HIV globally has continued to increase. By the end of 2005 there were approximately 40.3 million people living with HIV/AIDS, an increase from nearly 37.5 million in 2003. An estimated 5 million people were newly infected with HIV in 2005. In the same year more than 3 million died of AIDS-related illness; more than 500,000 of these were children.6

COMPLETE HIV 1/2

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HIV infection, AIDS and AIDS related complex have become a leading cause of illness and death in the United States for the past two decades. As of December 2001, a total of 774,467 per-sons were reported with AIDS and 448,060 of these persons had died. Approximately 800,000 – 900,000 persons in the United States are infected with HIV and approximately 80,000 - 280,000 of these persons may not be aware of their infected status.7

The HIV virus consists of a genomic RNA molecule protected by a capsid and an envelope. The HIV envelope is the major target for a humoral antibody response. The presence of the virus in patients causes the immune system to elicit the production of antibodies. The detection of these antibodies can be used as a diagnostic tool.

Enzyme Immunoassays (EIAs), Western Blots (WB), Nucleic Acid Amplification Test (NAT) assays and various other test systems are currently available for detection of HIV-1 and HIV-2 infec-tion.8-12 The Clearview® COMPLETE HIV 1/2 assay utilizes immobilized antigens for the detection of antibodies to HIV-1 and HIV-2, and is a point-of-care test to aid in the diagnosis of infection with HIV-1 and HIV-2.

BIOLOGICAL PRINCIPLES OF THE TESTThe Clearview® COMPLETE HIV 1/2 assay employs a unique combination of a specific antibody binding protein which is conjugated to colloidal gold dye particles, and HIV-1/2 antigens which are bound to the solid phase membrane. The venous or capillary (fingerstick) whole blood, serum or plasma is applied to the capillary tip of the Sampler of test device. The Sampler is inserted into the Buffer, which is provided in a sealed vial. The Buffer facilitates the lateral flow of the speci-men and test reagents and promotes the binding of the antibodies to the antigen. The specimen/buffer mixture migrates along the test strip by capillary action, reconstituting the conjugate. If present, the antibodies bind to the colloidal gold conjugated antibody binding protein. In a reac-tive sample, the dye conjugated-immune complex migrates on the nitrocellulose membrane and is captured by the antigens immobilized in the TEST area producing a pink/purple line. In the absence of HIV-1 and HIV-2 antibodies, there is no pink/purple line in the TEST area. The sample continues to migrate along the membrane and produces a pink/purple line in the CONTROL area containing immunoglobulin G antigens. This procedural control serves to demonstrate that speci-men and reagents have been properly applied and have migrated through the device.

MATERIALS PROVIDEDEach Kit contains the components to perform 25 tests:1 Product Insert for the Clearview® COMPLETE HIV 1/2 assay25 Copies of Subject Information Notice25 Disposable Test Stands (A)25 Pouches, each containing: •SamplerwithaTestStripinside (B) •BufferVialattachedtotheSampler(~350μL) (C) •SterileSafetyLancet (D) •Bandage (E) •DesiccantPacket (F)

Clearview® COMPLETE HIV 1/2 3

MATERIALS REQUIRED AND AVAILABLE AS AN ACCESSORY TO THE KIT Clearview® HIV Reactive/Nonreactive Controls (Catalog # 92112). Each package contains: 1 HIV 1 Reactive Control (0.25mL)1 HIV 2 Reactive Control (0.25mL)1 Nonreactive Control (0.25mL) 1 Product Insert

MATERIALS REQUIRED BUT NOT PROVIDED• Clock,watch,orothertimingdevice• Pipettorcapableofdelivering2.5μLofsample(forotherthanfingerstickorvenipuncturewhole

blood specimens)• Disposablegloves• Sterilegauze• Antisepticwipes• Biohazarddisposalcontainer• Collectiondevicesforsamplesotherthanfingerstickorvenipuncturewholebloodspecimens

WARNINGSFor IN VITRO diagnostic use

1. Read the Product Insert completely before using this assay. Follow the instructions carefully as not doing so may result in inaccurate Test Results.

2. Users of this test should follow the CDC Universal Precautions for prevention of transmission of Human Immunodeficiency Virus, Hepatitis B Virus, and other bloodborne pathogens.1

3. Use of this test Kit with specimen types other than those specifically approved for use with this device may result in inaccurate Test Results.

4. This test is CLIA-waived for use only with fingerstick whole blood and venipuncture whole blood samples.

5. This test should be performed at 18 to 30°C (64 to 86°F). If stored refrigerated, ensure that the pouch is brought to operating temperature before performing testing.

6. If the test Kit is stored at temperatures outside the storage temperature 8 to 30°C (46 to 86°F), or used outside the operating temperature 18 to 30°C (64 to 86°F), use the Kit Controls to ensure proper performance of the test.

7. Individual infected with HIV-1 and/or HIV-2 who is receiving highly active antiretroviral therapy (HAART) may produce false negative results.

PRECAUTIONSSAFETY PRECAUTIONS1. Handle the specimens and materials contacting specimens as if capable of transmitting infection.2. Do not eat, drink or smoke in the area where specimens and kit reagents are handled. Avoid

any contact with hands, eyes or mouth during specimen collection and testing.3. Wear protective clothing such as laboratory coats, disposable gloves and eye protection when

handling specimens.4. Dispose of all specimens and materials used in the test procedure in a biohazard waste

container. Lancets should be placed in a puncture-resistant container prior to disposal. The recommended method of disposal of biohazard waste is autoclaving for a minimum of 1 hour at 121ºC. Disposable materials may be incinerated. Liquid wastes may be mixed with appropriate chemical disinfectants. A freshly prepared solution of 10% bleach (0.5% solution of sodium hypochlorite) is recommended. Allow 60 minutes for effective decontamination. NOTE: Do not autoclave solutions that contain bleach.

5. For additional information on biosafety, refer to “Universal Precautions for prevention of trans-mission of Human Immunodeficiency Virus, Hepatitis B Virus, and other bloodborne patho-gens”1 and “Updated U.S. Public Health Service Guidelines for the Management of Occupational Exposure to HBV, HCV, and HIV and Recommendations for Postexposure Prophylaxis.”13

6. Use 10% bleach or other appropriate disinfectant to wipe all spills. The bleach solution should be made fresh each day.

4 05901.05

HANDLING PRECAUTIONS1. The Clearview® COMPLETE HIV 1/2 assay device has a sample filter in the lower part of the

device and an absorbent pad in the upper part of the device within the barrel that encloses the test strip. Confirm the presence of the sample filter and absorbent pad prior to performing the test. If either is missing, DO NOT USE.

2. Do not use any device if the pouch has been perforated. Do not use the device if the Desiccant Packet is missing.

3. Each device is for single use only.4. Do not use the reagents beyond the expiration date printed on the pouch. Always check

expiration date prior to testing.5. Do not mix reagents from different lot numbers of Kits.6. To ensure accurate Test Results, the Sampler must be inserted into the Buffer Vial immediately

after the sample application.7. Adequate lighting is required to read the Test Results.

STORAGE The Clearview® COMPLETE HIV 1/2 assay should be stored in its unopened pouch at 8 to 30°C (46 to 86°F). Do not freeze. Do not open the pouch until you are ready to perform a test. When stored as indicated, test devices are stable until the expiration date marked on the pouch.

SPECIMEN COLLECTIONPriortospecimencollection,providetestsubjectswithSubjectInformationNoticeandpre-testcounselingaccordingtoCDCGuidelinesforRapidHIVTesting.7

The Clearview® COMPLETE HIV 1/2 assay is performed on fingerstick whole blood, venous whole blood, serum or plasma specimens.

FINGERSTICK WHOLE BLOOD:Prepare to perform the fingerstick blood collection procedure. Clean the finger of the person being tested with an antiseptic wipe. Allow the finger to dry thoroughly or wipe dry with a sterile gauze pad. Using a sterile lancet, puncture the skin just off the center of the finger and wipe away the first drop with sterile gauze and avoid squeezing the fingertip to accelerate bleeding as this may dilute the blood with excess tissue fluid. Collect the sample from the second drop touching the Sampler tip of the device to the drop of blood until the Sampler tip is full. Test immediately, following Test Procedure Instructions.

VENOUS WHOLE BLOOD:Draw blood following laboratory procedures for obtaining venous blood. Collect sample in a tube containing citrate, heparin, or EDTA. Be sure the tube of blood is well mixed.

SERUM OR PLASMA:Note: Serum and Plasmamay only be tested in laboratories certified to runmoderatecomplexity tests.Draw blood following laboratory procedures for obtaining serum or plasma specimens. Collect specimen in a tube not containing any anticoagulant (serum), or in a tube containing citrate, heparin, or EDTA (plasma). Collect specimen in a clean container following standard laboratory procedures.

Venous whole blood, serum and plasma specimens may be tested immediately after collection. If specimens are not tested immediately, refrigerate them at 2 to 8°C (36 to 46°F) following col-lection. These specimens should be tested within 3 days of collection. If specimens are not tested within 3 days of collection, serum or plasma specimens should be frozen at -20°C (-4°F) or colder. DONOTFREEZEWHOLEBLOOD!

SPECIMEN SHIPPINGIf specimens are to be shipped, they should be packed in compliance with regulations covering the transportation of etiologic agents. Venous whole blood, serum and plasma specimens should be shipped refrigerated with cold packs or wet ice.


BufferCap Test

Stand

On a firm surface, drop theBuffer Cap in the Test Sample.

5. SPECIMEN APPLICATION WAIVED PROCEDURES

For fingerstick whole blood, touch blood drop with Sampler tip until the tip is full.

Alternately, pick up a drop of whole blood from the inside of a blood tube cap.

5. SPECIMEN APPLICATION MODERATELY COMPLEX PROCEDURE

For venous whole blood, serum or plasma, invert Sampler and pipet 2.5μL of specimeninto sampler tip.

2. WRITE PATIENT ID ON STAND

3. SEPARATE BUFFER CAP FROM TEST DEVICE

4. PLACE BUFFER CAP IN TEST STAND

1. OPEN POUCH, REMOVE AND IDENTIFY COMPONENTS

Identify Test Device, Buffer Cap and Test StandNote: If Desiccant Packet is missing or if absorbent pad (at top of Sampler) is missing or if sample filter (at bottom of Sampler) is missing, DO NOT USE. Discard device and use a new device.

Buffer Cap Test Stand (clear)Test Device

absorbent padsample filter

TESTPROCEDUREFORCLIAWAIVEDANDCLIAMODERATESETTINGSKIT COMPONENT PREPARATIONAll components for the Clearview® COMPLETE HIV 1/2 assay are ready to use as supplied. Follow directions as indicated. If the specimen to be tested is refrigerated, remove it from the refrigera-tor and allow it to come to a temperature of 18 to 30°C: (64 to 86°F) prior to testing.

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6. START THE TEST• With Buffer Cap in Stand, firmly press the

Device tip through foil cover.• Push hard until Device is fully seated in the Buffer Cap.

It will “snap” 3 times when properly seated. • Snap 1: through foil• Snap 2: into cap• Snap 3: fully seated

7. CONFIRM DEVICE IS FULLY SEATEDA. The blue line directly above the arrows must line up with the clear line in the StandB. You will see pink/purple Buffer solution begin to flow upwardsIF YOU DO NOT SEE PINK/PURPLE FLOW WITHIN 3 MINUTES, PUSH AGAIN!(then start timer)

READ TEST RESULTS Read the test between 15 and 20 minutes.

NOTE: Reactive Test Results (See Interpretation of Test Results section) may be observed and read earlier than 15 minutes. To verify a Nonreactive Test Result, wait theentire 15 minutes after starting the test.

Do not read results after 20 minutes.

8. START TIMING - WAIT FOR 15 MINUTES NOTE: the Sampler/ Buffer Vial should be kept

upright in the Test Stand15 minutes

INC

OR

REC

T

CORRECTLine inclear window

Control AreaTest Area

Confirmpink /purpleflow here


QUALITY CONTROLBUILT-IN CONTROL FEATUREThe control line serves as a built-in internal control and gives confirmation of sample addition and proper test performance. A pink/purple line will appear in the CONTROL area if the test has been performed correctly and the device is working properly (Please see section: Interpretation of Test Results).

EXTERNAL QUALITY CONTROLGood Laboratory Practices (GLP) necessitates testing external control material along with the test samples to ensure proper performance of the test Kit. Clearview® HIV Reactive/Nonreactive Controls (Catalog # 92112) are available separately for use with the Clearview® COMPLETE HIV 1/2 assay. The HIV Controls are used to verify the operator’s ability to properly perform the test and to interpret the results. Each Reactive Control will produce a REACTIVE Test Result and has been manufactured to produce a faint line in the TEST area. The Nonreactive Control will produce a NONREACTIVE Test Result. Run the Controls as per the TEST PROCEDURE and follow the instructions as described in INTERPRETATION OF TEST RESULTS sections of this Product Insert. It is the responsibility of each facility using the Clearview® COMPLETE HIV 1/2 assay to establish an adequate quality assurance program to ensure the performance of the device under specific locations and conditions of use.

RUN THE KIT CONTROLS UNDER THE FOLLOWING CIRCUMSTANCES:• Eachnewoperatorpriortoperformingtestsonpatientspecimens,• WhenopeninganewtestKitlot,• WheneveranewshipmentoftestKitsisreceived,• Ifthetemperatureoftheteststorageareafallsoutsideof8to30°C(46to86°F),• Ifthetemperatureofthetestingareafallsoutsideof18to30°C(64to86°F),• Atperiodicintervalsasindicatedbytheuserfacility.

If the HIV Control reagents do not produce the expected results, contact Alere™ Technical Support at (877) 441-7440.

INTERPRETATIONOFTESTRESULTSFORCLIAWAIVEDANDCLIAMODERATESETTINGSWhen the Clearview® COMPLETE HIV 1/2 assay is properly performed, the appropriate pink/purple lines will become visible. These are:

1. TheCONTROLLINE - which appears closer to the top of the test strip, indicates that specimen was adequately applied, and there was proper hydration and migration of reagents. The control line will become visible within 15 minutes after starting the test regardless of the HIV antibody status of the specimen.

2. TheTESTLINE - which appears closer to the bottom of the test strip (below the control line) indicates the presence of HIV-specific antibodies. The test line will only become visible within 15 minutes after starting a valid test when HIV specific antibodies are present at detectable levels in the specimen.

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NONREACTIVE (diagram 1):One pink/purple line in the CONTROL area, with no line in the TEST area indicates a NONREACTIVE Test Result. A NONREACTIVE Test Result means that HIV-1 and HIV-2 antibodies were not detected in the specimen. The Test Result is interpreted as NEGATIVE for HIV-1 and HIV-2 antibodies. However, this does not exclude possible infection with HIV. Follow CDC guidelines to inform the test subject of the Test Result and its interpretation.7,14

REACTIVE (diagram 2): Two pink/purple lines, one in the TEST area and one in the CONTROL area indicate a REACTIVE Test Result. The line in the TEST area may look different from the line in the CONTROL area. Intensities of the Test and Control Lines may vary. Test Result with visible lines in both TEST and CONTROL areas, regardless of intensity, is considered REACTIVE. A REACTIVE Test Result means that HIV-1 and/or HIV-2 antibodies have been detected in the specimen. The Test Result is interpreted as Preliminary POSITIVE for HIV-1 and/or HIV-2 antibodies. Follow CDC guidelines to inform the test subject of the Test Result and its interpretation. 7,14

INVALID (diagram 3):

A pink/purple line should always appear in the CONTROL area, whether or not a line appears in the TEST area. If there is no distinct pink/purple line visible in the CONTROL area (see diagrams 1 and 2), then the test is INVALID. Any line that appears outside of the Control Area or Test Area (see diagram 3) is an INVALID test. An INVALID test cannot be interpreted. It is recommended that the INVALID test be repeated with a new device.

INVALID (diagram 4):

One pink/purple line in the CONTROL area, with Test line outside the TEST area, then test is INVALID. It is recommended that the INVALID test be repeated with a new device.

LIMITATIONS OF THE PROCEDURE1. The Clearview® COMPLETE HIV 1/2 test must be used in accordance with the instructions in

this Product Insert to obtain accurate results.2. The Clearview® COMPLETE HIV 1/2 assay must be used with capillary (fingerstick) or

venous whole blood, serum or plasma only. Use of other types of specimens or testing of venipuncture whole blood specimens collected using a tube containing an anticoagulant other than citrate, heparin or EDTA may not yield accurate results. For serum samples, collect blood without anticoagulant.

3. Reading Nonreactive Test Results earlier than 15 minutes or any Test Result later than 20 minutes may yield erroneous results.

4. Do not open the sealed foil pouch until just prior to use.5. Do not use Kit contents beyond labeled expiration date.6. For the collection of the fingerstick whole blood specimen, ensure that finger is completely

dry before performing fingerstick.7. Read results in a well-lit area.

NONREACTIVE1 line

REACTIVE2 lines

INVALIDTest line

outside area

INVALIDNo control line,or outside area

Control area

Test area

1

CT

2 3 4


8. A Reactive Test Result using the Clearview® COMPLETE HIV 1/2 test suggests the presence of antibodies to HIV-1 and/or HIV-2 in the specimen. The Clearview® COMPLETE HIV 1/2 assay is intended as an aid in the diagnosis of infection with HIV-1/2. AIDS and AIDS-related conditions are clinical syndromes and their diagnosis can only be established clinically.

9. For a Reactive Test Result, the intensity of the test line does not necessarily correlate with the titer of antibody in the specimen.

10. A person who has antibodies to HIV-1 or HIV-2 is presumed to be infected with the virus, except that a person who has participated in an HIV vaccine study may develop antibodies to the vaccine and may or may not be infected with HIV.

11. A Nonreactive Test Result does not preclude the possibility of exposure to HIV or infection with HIV. An antibody response to recent exposure may take several months to reach detectable levels.

12. This assay has not been evaluated for newborn screening, cord blood specimens, or individuals less than 13 years of age.

PERFORMANCE CHARACTERISTICSThe Clearview® COMPLETE HIV 1/2 assay was evaluated in prospective clinical studies at four geographically distinct sites. The specimens were tested from three groups of individuals: Known infected with HIV-1, at high risk for infection with HIV-1, and at low risk for infection with HIV-1. The Clearview® COMPLETE HIV 1/2 assay was tested in parallel on fingerstick whole blood, venous whole blood, serum and plasma specimen matrices. No discordant result was obtained from all specimen matrices. The serum/plasma specimens from study subjects were also tested using a licensed Enzyme Immunoassay (EIA). Specimens with discordant results were further tested using licensed Western Blot and/or FDA approved NAT assay.

SENSITIVITYThe sensitivity of the Clearview® COMPLETE HIV 1/2 assay to detect infection with HIV-1 was evaluated using 614 specimens from individuals known to be infected with HIV-1 and from 776 individuals at high risk for infection with HIV-1 (Table 1). 648 individuals were identified as positive for infection with HIV-1 using a licensed confirmatory assay, and/or FDA approved NAT assay. Of these, 646 specimens tested reactive on the Clearview® COMPLETE HIV 1/2 assay. The calculated sensitivity of Clearview® COMPLETE HIV 1/2 assay in these studies was 99.7% (646/648 = 99.7% with 95% CI = 98.9% - 100%).

TABLE 1DetectionofantibodytoHIV-1 inspecimensfromindividualsknowntobe infectedwithHIV-1,andathighriskforinfectionwithHIV-1

Study Population

Samples Clearview® COMPLETE HIV 1/2 Reactive

Licensed EIA Repeatedly

Reactive

Licensed WB Reactive

True Positive1

Known Positive 614 610 612 612 612

High-Risk 776 36 41 352 363

Total 1390 646 653 647 648

1. Based on licensed WB and NAT assay results (when positive and EIA is repeatedly reactive). 2. Two specimens were indeterminate by Western Blot (one was initially reactive only on EIA

and nonreactive on Clearview® COMPLETE HIV 1/2, and one was repeatedly reactive on EIA and nonreactive on Clearview® COMPLETE HIV 1/2).

3. One specimen was repeatedly reactive on EIA and reactive on Clearview® COMPLETE HIV 1/2, indeterminate on WB, and positive on NAT.

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The sensitivity of the Clearview® COMPLETE HIV 1/2 assay to detect HIV-2 antibody was deter-mined by testing 202 serum/plasma specimens that were positive for HIV-2 antibodies only. These specimens were obtained from repository sources. A total of 488 specimens from an area endemic for HIV-2 infection were also tested (Table 2). All specimens reactive with the Clearview® COMPLETE HIV 1/2 in these studies were also reactive by a licensed anti-HIV-1/2 EIA. The sensitiv-ity of Clearview® COMPLETE HIV 1/2 for the detection of antibodies to HIV-2 in these studies was calculated to be 100% (203/203 = 100% with 95% CI = 98.2% - 100%).

TABLE 2DetectionofantibodytoHIV-2inknownHIV-2reactivespecimensandendemicsamples

Study Population Samples Clearview® COMPLETE HIV

1/2 ReactiveTrue HIV-2 Positive

Only1

Known HIV-2 Positive 202 202 202

Endemic Samples 488 272 1

TOTAL 690 229 203

1. Confirmation based on results using a research use HIV-2 Western blot.2. Of these 27 HIV-1 EIA and HIV-2 EIA reactive specimens; 23 were reactive on HIV-1 WB only,

three were reactive on HIV-1 and HIV-2 WB, and one was indeterminate on HIV-1 WB and reactive on HIV-2 WB.

REACTIVITYWITHHIV-1SPECIMENSFROMVARIOUSWORLDWIDEGEOGRAPHICREGIONSTo assess sensitivity of the Clearview® COMPLETE HIV 1/2 assay for HIV-1 specimens from various worldwide geographic regions, 750 confirmed HIV antibody-positive specimens were obtained. Of the 715 specimens evaluated from Africa, Asia, Latin America, Europe, and Belgium, 712 were reactive using Clearview® COMPLETE HIV 1/2. The remaining 35 confirmed positive specimens from two worldwide panels were evaluated, consisting of naturally occurring plasma speci-mens from diverse geographical locations (Spain, Ghana, Cote d’ Ivoire, Mozambique, Uganda, Zimbabwe, China, Thailand, India, USA and Argentina with HIV-1 genotypes: A, B, C, D, E, F, G, O, B/D and HIV-2). All 35 were reactive using Clearview® COMPLETE HIV 1/2 assay.

REACTIVITYWITHSEROCONVERSIONPANELSThe Clearview® COMPLETE HIV 1/2 assay was tested against 15 different seroconversion pan-els. Each panel consisted of sequential collections from a single individual who seroconverted. Samples were confirmed using Western Blot (WB) and two licensed EIA tests. As shown in Table 3, the Clearview® COMPLETE HIV 1/2 test performed similarly to currently licensed assays in detecting seroconversion.

TABLE 3ComparisonoftheClearview®COMPLETEHIV1/2assaytotwolicensedEIAassaysandWesternBlotindetectingseroconversion.(WhereNR=NonreactiveandRR=RepeatedlyReactive)

PanelRelative Day of

BleedClearview® COMPLETE

HIV 1/2 EIA 1 EIA 2 WB

PRB-927 (AB) 0 NR NR NR NR

28 NR RR NR NR





33 NR RR NR NR

35 R RR NR NR

40 R RR RR R

PRB-928 (AC) 0 NR NR NR NR

111 NR RR NR NR

120 R RR RR R

125 R RR RR R

130 R RR RR R

PRB-930 (AE) 0 NR NR NR NR

3 NR NR NR NR

7 NR RR NR NR

10 NR RR RR IND

PRB-931 (AF) 0 NR NR NR NR

2 NR NR NR NR

7 NR NR NR NR

9 NR NR NR NR

15 NR NR NR NR

28 R RR NR NR

33 R RR RR IND

35 R RR RR R

42 R RR RR R

PRB-934 (AI) 0 NR NR NR NR

7 R RR NR IND

11 R RR RR IND

PRB-938 (AM) 0 NR NR NR NR

3 NR NR NR NR

9 NR RR NR IND

PRB-944 (AT) 0 NR NR NR NR

2 NR NR NR NR

7 NR NR NR NR

9 NR NR NR NR

14 R RR NR IND

16 R RR NR IND

PRB-959 (BI) 0 NR NR NR NR

7 NR NR NR NR

9 NR RR NR NR

14 R RR RR R

19 R RR RR R

21 R RR RR R

26 R RR RR R

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PRB-904 (D) 0 NR NR NR NR

21 NR NR NR NR

49 NR NR NR NR

92 R RR RR R

99 R RR RR R

PRB-910 (J) 0 NR NR NR NR

14 R NR NR NR

26 R RR RR R

28 R RR RR R

32 R RR RR R

35 R RR RR R

40 R RR RR R

PRB-914 (N) 0 R RR NR IND

4 R RR RR IND

7 R RR RR IND

25 R RR RR R

31 R RR RR R

PRB-916 (P) 0 NR NR NR NR

4 NR NR NR NR

9 NR NR NR NR

15 NR NR NR NR

30 R RR RR R

35 R RR RR R

PRB-917 (Q) 0 NR NR NR NR

53 NR NR NR NR

57 NR NR NR NR

60 N/A* RR NR NR

65 R RR NR IND

67 R RR NR IND

72 N/A* RR RR R

PRB-919 (S) 0 NR NR NR NR

9 R RR NR R

11 R RR RR R

PRB-922 (V) 0 NR RR NR NR

4 NR RR NR NR

7 R RR NR NR

11 R RR NR R

* N/A – Not Available


REACTIVITYWITHHIV-1LOWTITERPANELSA total of 30 specimens from two characterized Low Titer panels were used to evaluate the ability of the Clearview® COMPLETE HIV 1/2 assay to detect antibodies to HIV-1. The results of testing are presented in Table 4 and demonstrate that the Clearview® COMPLETE HIV 1/2 assay detected the presence of antibody in a manner similarly to one or both of the licensed EIAs.

TABLE 4Comparison of the Clearview® COMPLETE HIV 1/2 assay to two licensed EIA assays andWestern Blot using Low Titer panels (Where NR = Nonreactive and RR = RepeatedlyReactive)

Panel Clearview® COMPLETE


PRB107-1 NR RR NR NR

PRB107-2 NR RR RR IND


PRB107-4 NR RR RR NR

PRB107-5 NR NR NR NR

PRB107-6 R RR RR NR


PRB107-8 NR RR RR NR


PRB107-10 R RR RR NR

PRB107-11 R RR RR R


PRB107-13 NR RR NR IND

PRB107-14 R RR RR R

PRB107-15 R RR RR IND

PRB108-1 R RR RR R



PRB108-4 R RR RR R

PRB108-5 R RR RR R


PRB108-7 R RR RR R

PRB108-8 R RR RR R

PRB108-9 R RR RR R


PRB108-11 R RR RR R




PRB108-15 RR RR RR IND

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REACTIVITYWITHHIV-1MIXEDTITERPANELSThe sensitivity of Clearview® COMPLETE HIV 1/2 assay was evaluated by testing three well charac-terized panels composed of specimens ranging from nonreactive to strong reactive for anti-HIV-1 antibody. The results are presented in Table 5 and indicate that the Clearview® COMPLETE HIV 1/2 assay was able to detect antibodies to HIV-1 similarly to the licensed EIA and WB.

TABLE 5ComparisonoftheClearview®COMPLETEHIV1/2assaytotwolicensedEIAassaysandWesternBlotusingMixedTiterPanels(WhereNR=NonreactiveandRR=RepeatedlyReactive)




PRB202-2 R RR RR R

PRB202-3 R RR RR R

PRB202-4 R RR RR R

PRB202-5 R RR RR R

PRB202-6 R RR RR R

PRB202-7 R NR RR R

PRB202-8 R RR RR R


PRB202-10 R RR RR R

PRB202-11 R RR RR R

PRB202-12 R RR RR R

PRB202-13 R RR RR R

PRB202-14 R RR RR R

PRB202-15 R RR RR R

PRB202-16 R RR RR R

PRB202-17 R RR RR R

PRB202-18 R RR RR R

PRB202-19 R RR RR R

PRB202-20 R RR RR R


PRB202-22 R RR RR R


PRB202-24 R RR RR R

PRB202-25 R RR RR R

PRB203-1 R RR RR R

PRB203-2 R RR RR R



PRB203-5 R RR RR R

PRB203-6 R RR RR R

PRB203-7 R RR RR R




PRB203-8 R RR RR R

PRB203-9 R RR RR R

PRB203-10 R RR RR R

PRB203-11 R RR RR R

PRB203-12 R RR RR R

PRB203-13 R RR RR R


PRB203-15 R RR RR R

PRB203-16 R RR RR R

PRB203-17 R RR RR R

PRB203-18 R RR RR R

PRB203-19 R RR RR R


PRB203-21 R RR RR R

PRB203-22 R RR RR R

PRB203-23 R RR RR R

PRB203-24 R RR RR R

PRB203-25 R RR RR R


PRB204-2 R RR RR R


PRB204-4 R RR RR R

PRB204-5 R RR RR R

PRB204-6 R RR RR R

PRB204-7 R RR RR R

PRB204-8 R RR RR R



PRB204-11 R RR RR R

PRB204-12 R RR RR R


PRB204-14 R RR RR R

PRB204-15 R RR RR R

PRB204-16 R RR RR R

PRB204-17 R RR RR R


PRB204-19 R RR RR R

PRB204-20 R RR RR R

PRB204-21 R RR RR R

PRB204-22 R RR RR R




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SPECIFICITYThe specificity of Clearview® COMPLETE HIV 1/2 assay was evaluated by testing specimens from low risk and high risk populations for infection with HIV-1 from three clinical study sites. The results are summarized in Table 6.

TABLE 6Performance of the Clearview® COMPLETE HIV 1/2 assay on specimens from individualspresumedtobenegativeforHIV-1infection

StudyPopulation

SamplesClearview®

COMPLETE HIV 1/2 assayNonreactive

LicensedEIANonreactive

TrueNegative1

Low-Risk 691 690 6872 691

High-Risk 776 740 7353 740

Total 1467 1430 1422 1431

1. Confirmation performed by licensed HIV-1 Western Blot, IFA or NAT. One specimen was EIA repeatedly reactive, WB indeterminate, and NAT positive. One specimen was EIA repeatedly reactive and WB indeterminate. These two specimens were not included in the specificity calculations.

2. Four specimens were repeatedly reactive on EIA and nonreactive on Clearview® COMPLETE HIV 1/2 assay and Western Blot.

3. Five specimens were repeatedly reactive on EIA and nonreactive on Clearview® COMPLETE HIV 1/2 assay and Western Blot.

Based on these studies, the specificity of Clearview® COMPLETE HIV 1/2 assay in these studies was calculated to be 99.9% (1430/1431 = 99.9% with 95% CI = 99.6% - 100%).

EFFECT OF POTENTIALLY INTERFERING SUBSTANCES AND UNRELATED MEDICAL CONDITIONSTo evaluate the influence of unrelated medical conditions or interfering substance on the speci-ficity and sensitivity of the Clearview® COMPLETE HIV 1/2 assay, 208 specimens representing unrelated medical conditions, and 110 specimens representing potential interfering substances were tested (Table 7). The specimens were spiked with either saline (Nonreactive) or an HIV-1 reactive serum specimen to a low level of reactivity. All HIV-1 spiked specimens gave reactive results, while all unspiked samples, with the exception of one elevated albumin specimen and 14 syphilis specimens, gave nonreactive results. The one elevated albumin specimen and all of the 14 unspiked syphilis specimens with reactive test results were subsequently confirmed as infected with HIV-1 using a licensed Western Blot assay. An additional ten known HIV-1 nonreac-tive, syphilis reactive specimens were tested and yielded expected results.

TABLE 7Clearview®COMPLETEHIV1/2assayreactivityagainstspecimensfromunrelatedmedicalconditionsorcontainingpotentialinterferingsubstances.

Clearview®COMPLETEHIV1/2assay

Description Saline (Nonreactive) HIV-1/2 (Weak Reactive)

Cirrhosis 20 / 20 20 / 20

CMV IgM 20 / 20 20 / 20

Recent flu vaccination1 11 / 11 11 / 11

HBV 21 / 21 21 / 21

HCV 19 / 19 19 / 19

HTLV-I 11 / 11 11 / 11


Clearview®COMPLETEHIV1/2assay

Description Saline (Nonreactive) HIV-1/2 (Weak Reactive)

HTLV-II 10 / 10 10 / 10

Multiparous 9 / 9 9 / 9

Myeloma 10 / 10 10 / 10

Rheumatoid Factor 10 / 10 10 / 10

Syphilis2 15 / 29 29 / 29

Tuberculosis 38 / 38 38 / 38

Elevated Albumin3 9 / 10 10 / 10

Elevated Bilirubin 10 / 10 10 / 10

Citrate 10 / 10 10 / 10

DNA 10 / 10 10 / 10

EDTA 10 / 10 10 / 10

Hemolyzed 10 / 10 10 / 10

Heparin 10 / 10 10 / 10

Icteric 10 / 10 10 / 10

Lipemic 10 / 10 10 / 10

Elevated Protein 10 / 10 10 / 10

Elevated Triglycerides 10 / 10 10 / 10

1. Collected within 6 months of vaccination2. Fourteen samples were confirmed reactive, using a licensed WB assay3. One sample was confirmed as containing HIV antibodies by using a licensed WB assay REPRODUCIBILITY STUDIESReproducibility was tested at three independent sites using three lots of Clearview® COMPLETE HIV 1/2 assay. A panel of five blinded samples representing nonreactive, low reactive HIV-1, low reactive HIV-2, high reactive HIV-1 and high reactive HIV-2 were run on three separate days by three separate technicians at each site. Testing was performed according to the Product Insert of the Clearview® COMPLETE HIV 1/2 test. Results were read at 15 minutes. Results were read semi-quantitatively using a common strip evaluation scale. A total of 405 data points was taken. There was 100% reproducibility (405/405) across all parameters.

RESULTS FROM UNTRAINED USER STUDYAn ‘untrained user’ study was conducted in which participants were given only the written test instructions and asked to perform testing on a masked panel of six whole blood specimens pre-pared at three different levels (negative, low positive and strong positive Clearview® COMPLETE HIV 1/2 assay reactivity). Study participants received no verbal or other instructions or training. The study protocol stipulated that professionally trained medical laboratory personnel or persons with prior experience using the Clearview® COMPLETE HIV 1/2 assay were excluded from participation. A total of 111 participants were enrolled from a total of four sites, representing a diverse demographic (educational, age, gender, ethnic, etc.). In order to help evaluate ease of use and clarity of the test instructions and interpretation of results, each participant was asked to complete a questionnaire and offer comments about their experience with the test.

The overall rate of correct results was 99.1% (636/642). The results of the study by specimen type are summarized below in Table 8. The overall rate of invalid results for all four sites was 3.5%.

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TABLE 8UntrainedUsersRateofCorrectTestResults

NonReactive LowReactive HighReactive Overall

99.1% (213/215) 98.1% (206/210) 100% (217/217) 99.1% (636/642)

95% CI = 96.7% - 99.9%

95% CI = 95.2% - 99.5%

95% CI = 98.3% - 100%

95% CI = 98.0% - 99.7%

REFERENCES1. Centers for Disease Control and Prevention (CDC) Universal Precautions for prevention of transmission of human

immunodeficiency virus, hepatitis B virus, and other bloodborne pathogens in health-care settings. MMWR 1988; 37(24):377-388.

2. Essex, M. (1999) Human immunodeficiency viruses in the developing world. Adv Virus Res 53 : 71-88.3. Kanki, P.J., Hopper, J.R. and Essex, M. (1987) The origins of HIV-1 and HTLV-4/HIV/2. Ann N Y Acad Sci 511 : 370-375.4. Nicoll, A., Gill, O.N. (1999) The global impact of HIV infection and disease. Commun Dis Publ Health 2 : 85-95.5. Valdiserri R.O., Holtgrave, D.R., West, G.R. (1999) Promoting early diagnosis and entry into care. AIDS 13 : 2317-2330.6. UNAIDS / WHO Press Release (2005) HIV Infection Rates Decreasing in Several Countries but Globally Number of People

Living with HIV Continue to Rise. Available at www.unaids.org/epi/2005/doc/docs/PR EpiUpdateNov05en.pdf: 1-3.7. CDC. Revised Guidelines for HIV Counseling, Testing and Referral and Revised Recommendations for HIV Screening of

Pregnant Women. MMWR 2001; 50(19);32-35.8. Essex, M., Kanki, P. J., Marlink, R., et al. (1990) Antigenic characterization of the human immunodeficiency viruses. J Am

Acad Dermatol 22 : 1206-1210.9. Essex, M., McLane, M.F., Lee, T.H. et al. (1983) Antibodies to cell membrane antigens associated with human T-cell

leukemia virus in patients with AIDS. Science 220 : 859-862.10. Gallo, R.C., Saluahuddin, S.Z., Popovic, M., et al. (1984) Frequent detection and isolation of cytopathic retroviruses (HTLV-

III) from patients with AIDS and at risk for AIDS. Science 224 : 500-503.11. Kenealy, W., Reed, D., Cybulsky, R., et.al. (1987) Analysis of human serum antibodies to human immunodeficiency virus

(HIV) using recombinant ENV and GAG antigens. AIDS Res Human Retrovir 3:95-105.12. Kovacs, A., Xu, J., Rasheed, S., et al. (1995) Comparison of a rapid non-isotopic polymerase chain reaction assay with four

commonly used methods for the early diagnosis of human Immunodeficiency Virus type 1 infection in neonates and children. Pediatr Infect Dis J 14 : 948-954.

13. CDC:Updated U.S. Public Health Service Guidelines for the Management of Occupational Exposures to HBV, HCV and HIV Recommendations for Postexposure Prophylaxis. MMWR 2001; 50(RR-11):1-42.

14. CDC: Approval of a New Rapid Test for HIV Antibody. MMWR 2002; 51 (46) 1051-1052.

ORDERINFORMATIONANDTECHNICALASSISTANCE:(877) 441-7440(321) 441-7200Clearview® COMPLETE HIV 1/2: Product No. 92111Clearview® HIV Reactive/Nonreactive Controls: Product No. 92112


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Manufactured by Chembio Diagnostic Systems, Inc., Medford, NY, for Alere under U.S. Patent No. 5,935,864, owned by StatSure Diagnostic Systems, Inc., Framingham, MA; and U.S. Patent Nos. 5,622,871; 5,656,503; 5,714,389; 6,187,598; 6,228,660; and 6,485,982, owned or licensed by the Alere group of companies.

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